Linked Life Data

20975664

Source:http://linkedlifedata.com/resource/pubmed/id/20975664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-12
pubmed:abstractText
Although anti-CD20 monoclonal antibodies (mAbs) show promise for the treatment of chronic lymphocytic leukemia (CLL), the success of the anti-CD20 mAb rituximab in CLL treatment has been limited. Novel anti-CD20 mAbs with more potent cytotoxic activity have recently been engineered, but so far most have only been tested in vitro with natural killer (NK) cells from healthy donors. Because it is still unclear whether these optimized cytotoxic mAbs will improve NK-cell killing of tumor cells in CLL patients, we characterized the relevant phenotypic and functional features of NK cells from CLL patients in detail. Expression of inhibitory and activating NK-cell receptors and of Fc gamma receptor IIIA (Fc?RIIIA) is well preserved in CD16(+)CD56(dim) cytotoxic NK cells from these patients, independently of disease progression. These cells are fully functional following cytokine stimulation. In addition, the Fc?RIIIA-optimized LFB-R603 anti-CD20 mAb mediates 100 times greater antibody-dependent cell-mediated cytotoxicity by NK cells from CLL patients and healthy donors than rituximab. Enhanced degranulation against autologous B-CLL cells is observed at lower concentrations of LFB-R603 than rituximab, regardless of CLL prognostic factors. These findings strongly justify further clinical development of anti-CD20 mAbs optimized for Fc?R engagement in CLL patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5551
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
101-9
pubmed:meshHeading
pubmed-meshheading:20975664-Adult, pubmed-meshheading:20975664-Aged, pubmed-meshheading:20975664-Aged, 80 and over, pubmed-meshheading:20975664-Antibodies, Monoclonal, pubmed-meshheading:20975664-Antibodies, Monoclonal, Murine-Derived, pubmed-meshheading:20975664-Antibody-Dependent Cell Cytotoxicity, pubmed-meshheading:20975664-Antigens, CD56, pubmed-meshheading:20975664-Antineoplastic Agents, pubmed-meshheading:20975664-Female, pubmed-meshheading:20975664-GPI-Linked Proteins, pubmed-meshheading:20975664-Humans, pubmed-meshheading:20975664-Immunophenotyping, pubmed-meshheading:20975664-Killer Cells, Natural, pubmed-meshheading:20975664-Leukemia, Lymphocytic, Chronic, B-Cell, pubmed-meshheading:20975664-Male, pubmed-meshheading:20975664-Middle Aged, pubmed-meshheading:20975664-Receptors, IgG
pubmed:year
2011
pubmed:articleTitle
Analysis of CD16+CD56dim NK cells from CLL patients: evidence supporting a therapeutic strategy with optimized anti-CD20 monoclonal antibodies.
pubmed:affiliation
INSERM, UMR-S 945, AP-HP, Hôpital Pitié-Salpêtrière, Service d'Hématologie Biologique, Paris, France. magali.legarff@psl.aphp.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't